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Nitrendipine and superoxide dismutase in ischemic renal injury
W K Jacobsen1, R M Schell, J S Matsumura
1Department of Anesthesiology and Critical Care Medicine, Loma Linda University, CA 92354.
Abstract:
The effect of the Ca entry blocker nitrendipine, the antioxidant superoxide dismutase (SOD), and a combination of nitrendipine and superoxide dismutase on postischemic renal function was studied in four groups (n = 24) of rats. The rats in group 1 (n = 6) were the ischemic control and received 10 mL of 0.9% NaCl. Group II (n = 6) received SOD 7.0 mg/kg. Group III (n = 6) received nitrendipine 1 mg/kg. Group IV (n = 6) received nitrendipine 1 mg/kg and SOD 7 mg/kg. After administration, both kidneys were rendered ischemic by cross-clamping the renal vessels for 60 min. Comparison of 24-h creatinine clearance (CCr) for 3 days after reversal of ischemia revealed: (a) nitrendipine alone was the most effective in preserving renal function (p < .05); (b) SOD provided some degree of improvement, but only on day 3 (p < .05); (c) a similar result was detected using a combination of nitrendipine and SOD (p < .05); (d) there was no significant difference between SOD and nitrendipine nor between SOD and the combination of nitrendipine/SOD; (e) there was a significant improvement with nitrendipine when compared to the combination of nitrendipine/SOD (p < .05).
Insights
Nitrendipine, a calcium entry blocker, significantly improved postischemic renal function in rats. Superoxide dismutase (SOD) offered some benefit, but nitrendipine alone was most effective.
Area of Science:
- Nephrology
- Pharmacology
- Biochemistry
Background:
- Ischemia-reperfusion injury significantly impairs renal function.
- Oxidative stress plays a key role in postischemic renal damage.
- Calcium entry blockers and antioxidants are potential therapeutic agents.
Purpose of the Study:
- To evaluate the renoprotective effects of nitrendipine and superoxide dismutase (SOD) in a rat model of renal ischemia.
- To compare the efficacy of nitrendipine alone, SOD alone, and their combination in preserving renal function post-ischemia.
Main Methods:
- Four groups of rats (n=24) were subjected to 60 minutes of renal ischemia.
- Groups received either saline (control), SOD (7.0 mg/kg), nitrendipine (1 mg/kg), or a combination of nitrendipine and SOD.
- Renal function was assessed by measuring 24-hour creatinine clearance (CCr) for three days post-ischemia.
Main Results:
- Nitrendipine monotherapy demonstrated the most significant preservation of renal function (p < .05).
- SOD administration showed a modest improvement in CCr, primarily on day 3 (p < .05).
- The combination of nitrendipine and SOD yielded results comparable to SOD alone, with nitrendipine alone showing superior efficacy (p < .05).
Conclusions:
- Nitrendipine is a highly effective agent for mitigating renal dysfunction following ischemia.
- While SOD offers some renoprotection, its combination with nitrendipine did not enhance the protective effect beyond nitrendipine alone.